Biomedical Engineering Reference
In-Depth Information
signaling between cells, and regulate the activities of secreted proteins, such as
growth factors. Some of the plasma membrane proteoglycans can bind cells to the
ECM and trigger the responses of cells to extracellular signals (Simons and
Horowitz
2001
; Yoneda and Couchman
2003
). GAG is an unbranched, negatively
charged, polysaccharide chain composed by repeating disaccharide units. The
main groups of GAGs of physiological signifi cance are hyaluronic acid (hyaluro-
nan), chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate.
Hyaluronan is unique among the GAGs because it does not contain any sulfate
and is a component of non-covalently formed complexes with proteoglycans in
the ECM. Hyaluronic acid polymers are very large (with molecular weights of
100-10,000 kDa) and can occupy a large volume. GAGs are located either in the
ECM or on the surface of cells, where these molecules serve as coreceptors to
help cells respond to secreted signal proteins (Raman et al.
2005
) . Due to high
viscosity and low compressibility, the mechanical characteristics of GAG are
ideal for excellent lubricators and shock absorbers and used as a lubricating fl uid,
for example, in the joints. Finally, examples of the tissue-specifi c components
include aggregans in the cartilage tissue or minerals (e.g., hydroxyapatite) in the
bone tissue.
2.2
ECM Architecture
Similar architectural characteristics of ECM can be found in the major tissue types,
such as nerve, muscle, epithelial, and connective tissues. Generally, the ECM is
made of various protein fi bers interwoven in a hydrated gel composed of proteogly-
cans and GAG chains (Fig.
1
). Fibrillar collagen forms the major matrix, strength-
ens the scaffold, and also provides substratum for cell adhesion. GAGs fi ll a large
volume and form highly hydrated gels in ECM. Adhesion proteins in the matrix and
on the surface of cell membrane bind macromolecules and cells to build up ECM
into an active and dynamic organization that can infl uence the cellular cytoskeleton
and cell spreading. The diversity of ECM in different tissues arises from the relative
amounts of the macromolecules mentioned above, tissue-specifi c components, and
the way in which they are arranged. For example, connective tissue and epithelial
tissue represent two extremes of contrasting spatial organization. In connective tis-
sue, cells are sparsely distributed within the ECM. Direct attachments between cells
are relatively rare, and the ECM is rich in fi brous polymers, especially collagens,
which bear most of the mechanical stress the tissue is subjected to. In contrast, epi-
thelial tissue has a scant ECM, consisting mainly of a thin mat called the basal
lamina, which underlies the epithelium. Cells are tightly bound together into sheets
called epithelia. The cells are attached to each other by cell-cell adhesions that bear
most of the mechanical stresses. Strong intracellular protein fi laments connect the
cells either to each other or to the underlying basal lamina. Examples would include
capillaries that consist of a single layer of endothelial cells attached to a basal
